An equivariant isomorphism theorem for mod p\mathfrak p reductions of arboreal Galois representations

Let $\phi$ be a quadratic, monic polynomial with coefficients in $\mathcal O_{F,D}[t]$, where $\mathcal O_{F,D}$ is a localization of a number ring $\mathcal O_F$. In this paper, we first prove that if $\phi$ is non-square and non-isotrivial, then there exists an absolute, effective constant $N_\phi$ with the following property: for all primes $\mathfrak p\subseteq\mathcal O_{F,D}$ such that the reduced polynomial $\phi_\mathfrak p\in (\mathcal O_{F,D}/\mathfrak p)[t][x]$ is non-square and non-isotrivial, the squarefree Zsigmondy set of $\phi_{\mathfrak p}$ is bounded by $N_\phi$. Using this result, we prove that if $\phi$ is non-isotrivial and geometrically stable then outside a finite, effective set of primes of $\mathcal O_{F,D}$ the geometric part of the arboreal representation of $\phi_{\mathfrak p}$ is isomorphic to that of $\phi$. As an application of our results we prove R. Jones' conjecture on the arboreal Galois representation attached to the polynomial $x^2+t$

A Genotypic-oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macro-categories of Cystic Fibrosis.

Cystic Fibrosis (CF) is a monogenic disease caused by mutations of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. The genotype-phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, 125 different mutated alleles (11 of which with novel mutations and 10 of which complex) and 225 genotypes were found. A strong correlation between mutational patterns at the genotypic level and phenotypic macro-categories emerged. This specificity appears to be largely dependent on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macro-categories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype - phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype - phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway

Autoimmune polyendocrine syndromes in the pediatric age

Autoimmune polyendocrine syndromes (APSs) encompass a heterogeneous group of rare diseases characterized by autoimmune activity against two or more endocrine or non-endocrine organs. Three types of APSs are reported, including both monogenic and multifactorial, heterogeneous disorders. The aim of this manuscript is to present the main clinical and epidemiological characteristics of APS-1, APS-2, and IPEX syndrome in the pediatric age, describing the mechanisms of autoimmunity and the currently available treatments for these rare conditions

Sexual developmental disorders in pediatrics

Disorders of sex development (DSD) are a heterogeneous group of pathologies that result in an alteration in sex determination or differentiation. DSD are estimated to affect 1: 4,500 newborns and according to the 2006 Chicago Consensus classification, DSD can be divided into three categories: those with a 46 XX karyotype, those with a 46 XY karyotype and those relating to sex chromosomes. It is crucial to correctly identify the pathology already in the first days of life to direct the patient and his family to the best path of care. For this reason, the role of the pediatrician is fundamental in the correct identification of the clinical picture and in supporting the family during the long process that involves the management of these patients. To make a diagnosis, it is necessary to follow a path led by a multidisciplinary team that includes several steps such as the execution of the genetic analysis, the evaluation with diagnostic imaging methods and laboratory evaluations. The therapeutic management, on the other hand, is still very complex even if in recent years we have moved from an attitude of early gender reassignment to an approach of watchful waiting to let the patient choose when she/he is mature enough to do so, which gender she/he feels to belong. It should not be forgotten that throughout this process the pediatrician must be both supportive and clinically active in the management of the child and his family

USE OF GAS CHROMATOGRAPHY ORAL CHROMA™ IN THE ASSESSMENT OF VOLATILE SULFUR COMPOUNDS FOR BREATH’S ANALYSIS IN ORAL AND GASTRIC AFFECTION

Introduction: Breathomics (Breath-based metabolomics) is a new biotechnology approach that allow us to diagnose some human diseases by the oral breath analysis.The method is based on the identi#cation and quanti#cation of volatile organic compound (VOC) in breath, by a new portable gas chromatography’s tools such as Oral Chroma®. This instrument is able to detect and quantify three different volatile sulfur compounds, VSC ( H2S, CH3S ,(CH3)2S) in 5 ml of oral breath, in fast time and with good analytical accuracy. In addition, different authors recently have been described as a comparative analysis of VSC could be useful in the diagnosis of different oral or systemic diseases such as: (i) oral tongue halitosis or/and gastric affection such as Helicobacter pylori infectio

Antioxidant properties of plant polyphenols in the counteraction of alcohol-abuse induced damage: impact on the mediterranean diet

Polyphenols are antioxidants contained in plants as olive and grape. As part of the Mediterranean diet, they may decrease the risk of cancer, of chronic and neurodegenerative diseases. Alcohol consumption plays a detrimental effect on health, causing tissue damage and disrupting the metabolism of Neurotrophins (NTs). NTs are crucial proteins for the life cycle of neuronal and non-neuronal cells. Alcohol abuse elicits changes in NTs levels in the brain and in other target organs, however, it was observed minor damage in animals early exposed to red wine, probably due to the antioxidant effects of polyphenols. Indeed, data show that resveratrol or other polyphenols extracted from the olive can effectively counteract serum free radicals’ formation caused by chronic alcohol intake, contrasting also alcohol-induced NTs liver elevation. The aim of the present review is to update pieces of evidences about the antioxidant properties of polyphenols and their role in counteracting alcohol-induced damage

DESIGNING OF A RT REAL TIME PCR ASSAY BASED ON NS1 GENE FOR RAPID DETECTION OF USUTU VIRUS (USUV)

Introduction: Usutu virus belongs to the Japanese encephalitis virus group (the isolates exhibited 97% identity) within the family Flaviviridae closely related to West Nile virus (WNV). Both share in nature an enzootic infectious cycle between avian hosts and mosquito vectors (i.e. Culex spp.). The distribution areal is expanding in several European countries, including Italy; the simultaneous spatial and temporal co-circulation of new flaviviruses require a new approaches in the laboratory diagnosis for Flaviviridae infection in humans

COVID-19 affects serum brain-derived neurotrophic factor and neurofilament light chain in aged men. Implications for morbidity and mortality

Background and Methods: Severe COVID-19 is known to induce neurological damage (NeuroCOVID), mostly in aged individuals, by affecting brain-derived neurotrophic factor (BDNF), matrix metalloproteinases (MMP) 2 and 9 and the neurofilament light chain (NFL) pathways. Thus, the aim of this pilot study was to investigate BDNF, MMP-2, MMP-9, and NFL in the serum of aged men affected by COVID-19 at the beginning of the hospitalization period and characterized by different outcomes, i.e., attending a hospital ward or an intensive care unit (ICU) or with a fatal outcome. As a control group, we used a novelty of the study, unexposed age-matched men. We also correlated these findings with the routine blood parameters of the recruited individuals. Results: We found in COVID-19 individuals with severe or lethal outcomes disrupted serum BDNF, NFL, and MMP-2 presence and gross changes in ALT, GGT, LDH, IL-6, ferritin, and CRP. We also confirmed and extended previous data, using ROC analyses, showing that the ratio MMPs (2 and 9) versus BDNF and NFL might be a useful tool to predict a fatal COVID-19 outcome. Conclusions: Serum BDNF and NFL and/or their ratios with MMP-2 and MMP-9 could represent early predictors of NeuroCOVID in aged men

Neuroinflammatory markers in the serum of prepubertal children with down syndrome

Down Syndrome (DS) is the most common chromosomal disorder. Although DS individuals are mostly perceived as characterized by some distinct physical features, cognitive disabilities, and cardiac defects, they also show important dysregulations of immune functions. While critical information is available for adults with DS, little literature is available on the neuroinflammation in prepubertal DS children. We aimed to evaluate in prepubertal DS children the serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), oxidative stress as free oxygen radicals defense (FORD), free oxygen radicals test (FORT), and cytokines playing key roles in neuroinflammation and oxidative processes as TNF-, TGF-β, MCP-1, IL-1, IL-2, IL-6, IL-10, and IL-12. No differences were found in NGF between DS children and controls. However, BDNF was higher in DS subjects compared to controls. We also did not reveal changes in FORD and FORT. Quite interestingly, the serum of DS children disclosed a marked decrease in all analyzed cytokines with evident differences in serum cytokine presence between male and female DS children. In conclusion, the present study evidences in DS prepubertal children a disruption in the neurotrophins and immune system pathways